OBJECTIVES:  Ovid and Embase.com are two search engines that are commonly used for searching the Medline and Embase databases.  The standard of practice for conducting a search for a systematic literature review seems to support the use of Ovid.  Our objective was to discern the advantages and disadvantages of both the Embase.com and Ovid search engines.  We sought to compare the two databases in the following ways: results of a search, and ease of searching. METHODS:  We conducted several searches to see if there were any differences in results.  We analyzed the variation in results to determine why the disparities existed.  We wrote a step-by-step search guide and highlighted the differences/difficulties encountered.  Using a set of written directions, we also asked researchers to conduct searches using both interfaces and rate ease of use on a scale of 0 through 5.  Research was also conducted through websites and help desks to ascertain the disparities in content between the two search engines. RESULTS:   There were differences in the search results between Ovid and Embase.com using the same search criteria.  The coding of articles sometimes differed, but there were very few, if any, relevant articles that were missed by either engine.  In terms of ease of use, Embase.com had lower scores indicating greater ease of use in searching, exporting into a reference manager, saving searches, and recalling data compared to Ovid.  In the research assessing the differences in content through the company websites, we found that Embase.com alleged to contain articles published further in the past, include more conference abstracts, and update Emtree terms more frequently than did Ovid. CONCLUSIONS:   There is no notable difference between Ovid and Embase.com in terms of search results when searching Embase and Medline.  However, Embase.com was rated as easier to use in several domains compared to Ovid.